A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.

Recently, we demonstrated that integrin adhesion to the extracellular matrix at the cleavage furrow is essential for cytokinesis of adherent cells. Here, we report that tight junction protein ZO-1 (Zonula Occludens-1) is required for successful cytokinesis in NCI-H460 cells plated on fibronectin. Th...

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Main Authors: Saara Hämälistö, Jeroen Pouwels, Nicola de Franceschi, Markku Saari, Ylva Ivarsson, Pascale Zimmermann, Andreas Brech, Harald Stenmark, Johanna Ivaska
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070696&type=printable
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author Saara Hämälistö
Jeroen Pouwels
Nicola de Franceschi
Markku Saari
Ylva Ivarsson
Pascale Zimmermann
Andreas Brech
Harald Stenmark
Johanna Ivaska
author_facet Saara Hämälistö
Jeroen Pouwels
Nicola de Franceschi
Markku Saari
Ylva Ivarsson
Pascale Zimmermann
Andreas Brech
Harald Stenmark
Johanna Ivaska
author_sort Saara Hämälistö
collection DOAJ
description Recently, we demonstrated that integrin adhesion to the extracellular matrix at the cleavage furrow is essential for cytokinesis of adherent cells. Here, we report that tight junction protein ZO-1 (Zonula Occludens-1) is required for successful cytokinesis in NCI-H460 cells plated on fibronectin. This function of ZO-1 involves interaction with the cytoplasmic domain of α5-integrin to facilitate recruitment of active fibronectin-binding integrins to the base of the cleavage furrow. In the absence of ZO-1, or a functional ZO-1/α5β1-integrin complex, proper actin-dependent constriction between daughter cells is impaired and cells fail cytokinesis. Super-resolution microscopy reveals that in ZO-1 depleted cells the furrow becomes delocalized from the matrix. We also show that PKCε-dependent phosphorylation at Serine168 is required for ZO-1 localization to the furrow and successful cell division. Altogether, our results identify a novel regulatory pathway involving the interplay between ZO-1, α5-integrin and PKCε in the late stages of mammalian cell division.
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publisher Public Library of Science (PLoS)
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spelling doaj-art-e5a853b910554d848bbd6ca318ccd87f2025-08-20T02:09:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7069610.1371/journal.pone.0070696A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.Saara HämälistöJeroen PouwelsNicola de FranceschiMarkku SaariYlva IvarssonPascale ZimmermannAndreas BrechHarald StenmarkJohanna IvaskaRecently, we demonstrated that integrin adhesion to the extracellular matrix at the cleavage furrow is essential for cytokinesis of adherent cells. Here, we report that tight junction protein ZO-1 (Zonula Occludens-1) is required for successful cytokinesis in NCI-H460 cells plated on fibronectin. This function of ZO-1 involves interaction with the cytoplasmic domain of α5-integrin to facilitate recruitment of active fibronectin-binding integrins to the base of the cleavage furrow. In the absence of ZO-1, or a functional ZO-1/α5β1-integrin complex, proper actin-dependent constriction between daughter cells is impaired and cells fail cytokinesis. Super-resolution microscopy reveals that in ZO-1 depleted cells the furrow becomes delocalized from the matrix. We also show that PKCε-dependent phosphorylation at Serine168 is required for ZO-1 localization to the furrow and successful cell division. Altogether, our results identify a novel regulatory pathway involving the interplay between ZO-1, α5-integrin and PKCε in the late stages of mammalian cell division.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070696&type=printable
spellingShingle Saara Hämälistö
Jeroen Pouwels
Nicola de Franceschi
Markku Saari
Ylva Ivarsson
Pascale Zimmermann
Andreas Brech
Harald Stenmark
Johanna Ivaska
A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
PLoS ONE
title A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
title_full A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
title_fullStr A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
title_full_unstemmed A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
title_short A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
title_sort zo 1 α5β1 integrin complex regulates cytokinesis downstream of pkcε in nci h460 cells plated on fibronectin
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070696&type=printable
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